Actions of bile salts and of papaverine and intracellular cyclic AMP in isolated rat uterus

Uruno, Tsutomu; Takayanagi, Issei; Kubota, Keiichi; Takagi, Keijiro

doi:10.1016/0014-2999(75)90330-1

Cited by 14 publications

(8 citation statements)

References 13 publications

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“…Similar effects of these bile salts on motor function have been described in vitro for the guinea pig ileum [Kubota, Urono, Kondo and Tomizawa, 1970] and the rat uterus [Urono, Takayanagi, Kubota and Takagi, 1975] at concentrations roughly the same as described here. The mode of action of the bile salts is a matter of speculation.…”

Section: Discussionsupporting

confidence: 55%

EFFECTS OF BILE SALTS ON THE MOTOR ACTIVITY OF THE GUINEA‐PIG GALL‐BLADDER IN VITRO

Rutishauser¹

1978

Exp Physiol

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Intra-luminal pressures were measured in in vitro preparations of the guinea-pig gall bladder. Intrinsic tone and spontaneous activity were recorded together with the response of the gall-bladder to Pancreozymin. The effect of the presence of a variety of conjugated and unconjugated bile salts in the luminal fluid [pH 7.4] was studied. Sodium deoxycholate and sodium chenodeoxycholate had in inhibitory effect on motor activity at concentrations as low as 6.0 times 10(-6) mol. 1(-1) Sodium taurocholate at a concentration of 3 times 10(-3) mol. 1(-1) promoted regular spontaneous activity. The results are discussed in relation to their possible physiological, pathological and pharmacological implications.

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Section: Discussionsupporting

confidence: 55%

EFFECTS OF BILE SALTS ON THE MOTOR ACTIVITY OF THE GUINEA‐PIG GALL‐BLADDER IN VITRO

Rutishauser¹

1978

Exp Physiol

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“…In addition, bile acids (30-300 M) have been shown to relax gallbladder smooth muscle (Sunagane et al, 1990;Xu et al, 1997), intestine (Sunagane et al, 1986), and uterus (Uruno et al, 1975). However, the cellular and molecular mechanisms underlying this widespread, nonspecific relaxation of smooth muscle by bile acids are not well understood.…”

Section: Possible Role Of Bile Acid Activation Of Bk Ca Channels In Bmentioning

confidence: 99%

Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells

Dopico

2002

The Journal of General Physiology

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Bile acids have been reported to produce relaxation of smooth muscle both in vitro and in vivo . The cellular mechanisms underlying bile acid-induced relaxation are largely unknown. Here we demonstrate, using patch-clamp techniques, that natural bile acids and synthetic analogues reversibly increase BK Ca channel activity in rabbit mesenteric artery smooth muscle cells. In excised inside-out patches bile acid-induced increases in channel activity are characterized by a parallel leftward shift in the activity-voltage relationship. This increase in BK Ca channel activity is not due to Ca 2 ϩ -dependent mechanism(s) or changes in freely diffusible messengers, but to a direct action of the bile acid on the channel protein itself or some closely associated component in the cell membrane. For naturally occurring bile acids, the magnitude of bile acid-induced increase in BK Ca channel activity is inversely related to the number of hydroxyl groups in the bile acid molecule. By using synthetic analogues, we demonstrate that such increase in activity is not affected by several chemical modifications in the lateral chain of the molecule, but is markedly favored by polar groups in the side of the steroid rings opposite to the side where the methyl groups are located, which stresses the importance of the planar polarity of the molecule. Bile acidinduced increases in BK Ca channel activity are also observed in smooth muscle cells freshly dissociated from rabbit main pulmonary artery and gallbladder, raising the possibility that a direct activation of BK Ca channels by these planar steroids is a widespread phenomenon in many smooth muscle cell types. Bile acid concentrations that increase BK Ca channel activity in mesenteric artery smooth muscle cells are found in the systemic circulation under a variety of human pathophysiological conditions, and their ability to enhance BK Ca channel activity may explain their relaxing effect on smooth muscle.

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“…Such a nonspecific spasmolytic action of bile salts have also been demonstrated in the intestine (Kimura et al, 1967;Kubota et al, 1970;) and the uterus (Uruno et al, 1974(Uruno et al, , 1975. Deoxycholate and ursodeoxycholate accelerated the 45Ca-efflux from the gallbladder partly depolarized by potassium when the drugs were applied to the muscle during the later efflux phase where intracellularly bound calcium ions were effluxed (Fig.…”

Section: Discussionmentioning

confidence: 60%

“…Uruno et al (1974) showed that bile salts could inhibit cyclic AMP phosphodiesterase (PDE) activity, resulting in the accumulation of cytoplasmic cyclic AMP. Good correlation between the increment of cyclic AMP level and the relaxant effects of bile salts was also found in the rat uterus (Uruno et al, 1975). Francavilla et al (1981) demonstrated the inhibition by bile salts of the cyclic AMP phosphodiesterase isolated from the human gallbladder.…”

Section: Introductionmentioning

confidence: 85%

Possible mechanisms of spasmolytic action of bile salts on the isolated guinea-pig gallbladder.

Sunagane

Kobori

Uruno

et al. 1990

Jpn. J. Smooth Muscle Res.

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Sunagane N., T. Kobori, T. Uruno and K. Kubota. Possible mechanisms of spasmolytic action of bile salts on the isolated guinea-pig gallbladder. The spasmolytic action of bile salts on gallbladder smooth muscle could explain the alleged relief of biliary colic seen during bile acid therapy. The mechanisms of spasmolytic action of bile salts, ursodeoxycholate and deoxycholate were studied in the isolated gallbladder of guinea-pigs.The bile salts accelerated the 45Ca-efflux from the gallbladder with synchronous relaxation and inhibited the cellular 45Ca-uptake by the depolarized muscle preparation. Further, they sensitively inhibited CaCl2-induced contraction of the depolarized muscle. The tissue cyclic AMP content of the gallbladder was significantly elevated by the bile salts. Dibutyryl cyclic AMP mimicked the effects of bile salts on the Ca-efflux and the muscle relaxation, but showed no effect on the cellular Ca-uptake. From these results, it is suggested that the bile salts produce the relaxant action through accelerating Ca-efflux, which is probably coupled with the elevation of the cellular cyclic AMP level, and through suppressing the Ca-influx across the cell membrane.

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Actions of bile salts and of papaverine and intracellular cyclic AMP in isolated rat uterus

Cited by 14 publications

References 13 publications

EFFECTS OF BILE SALTS ON THE MOTOR ACTIVITY OF THE GUINEA‐PIG GALL‐BLADDER IN VITRO

EFFECTS OF BILE SALTS ON THE MOTOR ACTIVITY OF THE GUINEA‐PIG GALL‐BLADDER IN VITRO

Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells

Possible mechanisms of spasmolytic action of bile salts on the isolated guinea-pig gallbladder.

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